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Modified dose intensive R- CODOX-M/IVAC for HIV-associated burkitt (BL) (AMC 048) shows efficacy and tolerability, and predictive potential of IRF4/MUM1 expression

  • Ariela Noy1Email author,
  • Lawrence Kaplan2,
  • Jeannette Lee3,
  • Ethel Cesarman4 and
  • Wayne Tam4
Infectious Agents and Cancer20127(Suppl 1):O14

Published: 19 April 2012


Overall SurvivalFebrile NeutropeniaTumor Lysis SyndromeHigh Relapse RateTreatment Related Mortality


HIV associated BL remains of concern for toxicity of dose-intensive regimens used in HIV negative patients (pts). Less intensive regimens have a high relapse rate. We modified CODOX-M/IVAC hoping to preserve efficacy while improving tolerability, particularly treatment related mortality (TRM). Primary object: improving 1 year overall survival (OS) from the historical 65 to 85%.


Modifications of the US NCI regimen include rituximab (R), cyclophosphamide reduction [800 mg/m2 x 2 days], vincristine 2 mg cap, methotrexate (mtx) 3000 mg/m2, dual chemotherapy lumbar punctures and IVAC infusion (high risk pts). Antibiotic prophylaxis & growth factor support specified, 100% grade IV hematopoietic toxicities in the original regimen. HAART therapy at the discretion of the local MD. Pathology review included CD20, CD10, BCL2, BCL6, p53, Ki67, BLIMP1, IRF4/MUM1 and EBV EBER. (Table 1)
Table 1

Table 1


N (%)

Treatment Completed per protocol

21 (62%)

Disease Progression

3 (9%)

Early termination due to adverse event*

5 (15%)

Early termination due to patient withdrawal**

2 (6%)

Early termination – counts did not recover within time frame to begin cycle 4

1 (3%)

Treatment ongoing

2 (6%)

*1 pt with grade (gr) 4 thrombocytopenia and gr 3 infection; 1 pt with gr 3 left hemiparesis; 1 pt with gr 3 confusion unrelated to treatment; 1 pt with prior hepatitis B and cirrohosis had gr 3 encephalopathy and pulmonary infiltrates; 1 pt with gr 4 neutropenia and gr4 thrombocytopenia.

**1 CR 2 yrs post treatment.


Accrual of 33 planned pts by April 2010. Baseline: Classical Burkitt, 97%; Low/High Risk, 9/91%; Median (range) Age 42 (19 – 55); CD4 count 195 (0 - 721), CD4 <100, 5 (27%); HIV viral load 1819 (Undetectable – 1,187,968). Median follow up (fu) is 9 mos for surviving pt. Number of pts with gr3/4 toxicity: any 20 (61%), 13 (39%) hematologic, 16 (48%) infection including 7 febrile neutropenia, 6 metabolic with 1 tumor lysis syndrome, 4 neurologic, 2 thrombotic and 1 each coagulation, GI or pain. Only 2 gr 1/2 stomatitis/mucositis; 0 had gr 3/4. Six deaths: encephalopathy with hepatic failure, hepatitis B and pneumonia (1), disease progression (3) including 1 in the CNS; fungal infection (1); HIV. Median 1 year OS (n=34) was 81.7% (61.0%, 92.1%) with a 35 mo median survival. OS by non-BL defining proteins: EBER +/- (8/16) and p53 +/- (10/10) were not predictive. IRF4/MUM1 +/- (8/15) highly predictive in overall pts, but not in the confirmed Burkitt +/- (6/14) with only 1 IRF4/MUM1 neg pt dying of BL.


AMC 048 with a median fu of 9 mos has a 1 yr OS of 82% in BL. Relapses after 1 year are rare. TRM was zero. R did not appear to increase toxicity. Only 5 pts withdrew due to AEs. Grade 3/4 toxicities were markedly reduced. Results compare favorably with 2 studies of HIV neg pts. Magrath (1995) reported 100% grade 4 hematologic and 20% grade 4 mucositis in 39 adults, 33 children (92% 2 yr EFS). MRC/NCRI LY10 trial (Mead 2008) reduced mtx (3gr/m2), but reported 9% TRM (64% 2 yr OS). IRF4/MUM1 deserves further study in BL.



This study is presented on behalf of the AIDS Malignancy Consortium.

Authors’ Affiliations

Memorial Sloan-Kettering Cancer Center, New York, USA
University of California, San Francisco, USA
University of Arkansas for Medical Sciences, Little Rock, USA
Weill Cornell Medical College and New York Presbyterian Hospital, New York, USA


© Noy et al; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.